NO EVIDENCE FOR PRESYNAPTIC OPIOID RECEPTORS ON CHOLINERGIC, BUT PRESENCE OF KAPPA-RECEPTORS ON DOPAMINERGIC-NEURONS IN THE RABBIT CAUDATE-NUCLEUS - INVOLVEMENT OF ENDOGENEOUS OPIOIDS

The effects of various opioid receptor agonists and antagonists were s tudied in rabbit caudate nucleus slices preincubated with either [H-3] dopamine or [H-3] choline, superfused with medium (containing in most experiments the D2 receptor antagonist domperidone) and subjected to e lectrical field stimulation. The stimulation-evoked [H-3]overflow from slices prelabeled with [H-3]dopamine (evoked [H-3]dopamine release) w as significantly reduced by preferential kappa-Opioid receptor agonist s, like U-50,488 H, but not by mu- or delta-opioid receptor selective drugs. Opioid receptor antagonists shifted the concentration/response curve of U-50,488 H to the right (apparent pA2-value of the kappa-sele ctive antagonist nor-binaltorphimine: 10.1) and enhanced the evoked do pamine release in the presence of a mixture of peptidase inhibitors. O n the other hand, the [H-3]overflow from rabbit caudate nucleus slices prelabeled with [H-3]choline (evoked acetylcholine release) remained almost unaffected by any opioid receptor agonist as long as the presyn aptic D2 heteroreceptor was blocked with domperidone: in the absence o f domperidone, U-50,488 H exhibited facilitatory effects. For comparis on, the effects of the preferential 6-opioid receptor agonist DPDPE wa s also studied in slices of the rat striatum, where it clearly inhibit ed the evoked acetylcholine release. From our data we conlude that in the rabbit caudate nucleus the evoked dopamine release is inhibited by both exogenous and endogenous opioids via presynaptic kappa-opioid re ceptors, whereas the evoked release of acetylcholine is not, or only i ndirectly (via released dopamine) affected by opioids.